Abstract
Reports on the association of TGF-β1 polymorphisms with breast cancer (BC) have been conflicting, inconsistent, inconclusive, and controversial. PubMed, EMBASE, and Google Scholar were used to identify studies on TGF-β1 polymorphisms and BC risk. Data were extracted independently, and of the initial 3043 studies, 39 case-control studies were eligible for inclusion in the meta-analysis. Information from these studies was extracted, and the overall associations of three TGF-β1 polymorphisms (TGF-β1 29>T/C, TGF-β1-509 C/T, and TGF-β1*6A) with BC risk were analyzed using overall allele, homozygous, heterozygous, recessive, and dominant models. None of the three TGF-β1 polymorphisms studied had a significant influence on the development of BC. However, stratified analysis revealed a positive correlation between the TGF-β1 29T>C polymorphism and BC risk according to a heterozygous model of the Asian population (odds ratio (OR) = 1.115, 95% confidence interval (CI) = 1.006–1.237, p = 0.039). Interestingly, this polymorphism was associated with lower odds of BC according to a heterozygous model of the Middle Eastern population (OR = 0.602, 95% CI = 0.375–0.966, p = 0.035). Thus, our analysis of large datasets indicates that the TGF-β1 29T>C polymorphism is significantly associated with BC risk in the Asian population. In contrast, the TGF-β1*6A and TGF-β1-509 C/T polymorphisms failed to show an association with BC.
Highlights
The transcription growth factor β (TGF-β) signaling pathway has been studied extensively in several cancer types, including breast cancer (BC)
TGF-β1 plays an important role in BC progression, metastasis, stemness, and chemo-resistance
High levels of TGF-β1, which are influenced by TGF-β1 polymorphisms, have been associated with cancer risk
Summary
The transcription growth factor β (TGF-β) signaling pathway has been studied extensively in several cancer types, including breast cancer (BC). The TGF-β superfamily consists of 33 structurally similar members, including bone morphogenic proteins (BMPs), TGF-β ligands, and activins, which play important roles in mammary development [1,2,3]. Isoforms of TGF-β ligands that are closely related both structurally and functionally (TGF-β1, TGF-β2, and TGF-β3) have been reported to modulate cell progression, migration, and apoptosis [4]. TGF-β exhibits both tumorigenic and tumor-suppressive roles [5]. Cancers 2020, 12, 471 a tumor suppressor during the early stages of cancer development, it exhibits oncogenic properties, inducing cell migration and invasion, during the later stages [2,6,7]. Researchers demonstrated that the TGF-β1 29T>C polymorphism increases the secretion of TGF-β levels [9]. Ziv et al demonstrated that CC genotype of the TGF-β1
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